The goal of the Neuropathology Core is to collect and characterize brain tissue, cerebrospinal fluid and blood from demented patients and their controls in order to support research programs related to AD and other dementias. The specific aims are to provide research-quality diagnostic evaluations; to prepare, evaluate and archive tissue from neuropsychologically characterized patients and their controls; and to create an enabling infrastructure for multidisciplinary research on the system-level distribution of neuropathological markers. During the first 4 years of the Northwestern ADC, the Neuropathology Core collected, analyzed and distributed nearly 140 autopsy cases and hundreds of plasma, blood, and DNA samples. A user-friendly relational database has been implemented for storing this information and integrating it with clinical information in ways that facilitate research queries. These resources have supported over 30 research projects and have led to more than 40 publications. A distinctive feature of this Neuropathology Core is its multidisciplinary integration of neuropathology, neurobiology and neuroanatomy in ways that foster a neural system approach to dementing diseases. This goal will be served through the recent acquisition of stereological equipment, the availability of whole-hemisphere brain sectioning, and the establishment of a Laboratory of Molecular Pathomorphology which will act as an incubator for studies where molecular insights or neuropsychological patterns need to be linked to histopathological findings. The Neuropathology Core will provide tissue for ongoing investigations related to amyloid, neuroglia, tau, ApoE and cholinergic pathways in AD. The principal source of tissue for the Neuropathology Core will be the Northwestern ADC. However, in order to augment the acquisition of specimens from neuropsycho-logically characterized patients and controls, the Neuropathology Core will also receive specimens from the Wealshire, a nursing home specializing in the care of dementia. Further specimens will come from the Miami Brain Endowment Bank, where Dr. Deborah Mash directs a cohort of over 600 individuals who have agreed to brain donation and who are non-demented when they enter a longitudinal study involving yearly neuropsychological evaluations. This diversity of autopsy sources will allow the Neuropathology Core to provide the tissue resources that are needed to support existing and prospective research projects related to AD and dementia.